Clinico-pathological factors associated with radioiodine refractory differentiated thyroid carcinoma status.

PURPOSE: Risk factors for developing radioiodine refractory thyroid cancer (RAIR-TC) have rarely been analyzed. The purpose of the present study was to find clinical and pathological features associated with the occurrence of RAIR-disease in differentiated thyroid cancers (DTC) and to establish an effective predictive risk score. METHODS: All cases of RAIR-DTC treated in our center from 1990 to 2020 were retrospectively reviewed. Each case was matched randomly with at least four RAI-avid DTC control patients based on histological and clinical criteria. Conditional logistic regression was used to examine the association between RAIR-disease and variables with univariate and multivariate analyses. A risk score was then developed from the multivariate conditional logistic regression model to predict the risk of refractory disease occurrence. The optimal cut-off value for predicting the occurrence of RAIR-TC was assessed by receiver operating characteristic (ROC) curves and Youden's statistic. RESULTS: We analyzed 159 RAIR-TC cases for a total of 759 controls and found 7 independent risk factors for predicting RAIR-TC occurrence: age at diagnosis ≥ 55, vascular invasion, synchronous cervical, pulmonary and bone metastases at initial work-up, cervical and pulmonary recurrence during follow-up. The predictive score of RAIR-disease showed a high discrimination power with a cut-off value of 8.9 out of 10 providing 86% sensitivity and 92% specificity with an area under the curve (AUC) of 0.95. CONCLUSION: Predicting the occurrence of RAIR-disease in DTC patients may allow clinicians to focus on systemic redifferentiating strategies and/or local treatments for metastatic lesions rather than pursuing with ineffective RAI-therapies.

Recurrent Middle Eastern Differentiated Thyroid Carcinoma Has Worse Outcomes Than Persistent Disease.

Background: Despite the excellent prognosis of differentiated thyroid carcinoma (DTC), recurrent and persistent disease remain major challenges. Emerging studies to differentiate between recurrent and persistent disease are controversial, with studies from the Middle East lacking. Methods: We retrospectively analyzed 1691 patients who underwent surgery ± I131 treatment for DTC, with a median age of 38.7 years and median follow-up of 95.3 months. Results: We found a similar prevalence rate for persistent and recurrent disease (17.7% vs. 17.9%) in Middle Eastern DTC patients. Relative to patients with persistent disease, patients with recurrent disease were significantly older (median age: 36.1 vs. 45.8 years; p < 0.0001) and were more likely to have ATA high-risk tumors (61.5% vs. 75.2%; p = 0.0003). On multivariate logistic regression analysis, both T and N status were independent predictors for recurrent as well as structural persistent disease. However, older age, bilaterality and extrathyroidal extension were independent predictors of recurrent disease alone. In addition, patients with recurrent disease had significantly worse cancer-specific survival (p < 0.0001), which remained significant in multivariate analysis. Conclusions: Although persistent and recurrent disease in Middle Eastern DTC have similar frequencies, recurrent disease has worse outcomes compared to persistent disease. Hence, differentiating recurrence from persistence has great potential clinical relevance for therapeutic and follow-up approaches, contributing to improving the outcomes of DTC patients of Middle Eastern ethnicity.

Pre-Treatment and Post-Treatment I-131 Imaging in Differentiated Thyroid Carcinoma.

Radioiodine imaging in initial perioperative settings, after the total thyroidectomy, includes pre-treatment and post-treatment radioiodine imaging. While the benefit of post-treatment whole-body imaging (PT-WBI) is well established, the role of diagnostic whole-body imaging (dx WBI), prior to radioiodine (I-131) ablative or therapeutic doses, is controversial. Dx WBI has been abandoned in most nuclear medicine centers long ago. Planar low-dose dxWBI provides the volume of postoperative thyroid remnants, but it cannot detect occult metastatic foci in the neck. The modern integrated multimodality, i.e., SPECT/CT imaging, provides three dimensional images and accurate anatomic/metabolic data. This hybrid technology offers better spatial resolution but not better sensitivity. Dx WBI has low theranostic power because of the radioiodine indifference and low detection sensitivity for small-volume nodal disease in the neck. Since dx WBI cannot clarify the paratracheal cervical uptake, thyroid remnants may be easily misinterpreted as nodal disease, leading to a false N upstaging (from N0 stage to N1 stage) in DTC patients. Post-ablation I-131 imaging has a significant role in the initial staging of radioiodine-avid DTC and in the identification of non-radioiodine avid tumors. Additionally, SPECT/CT in the post-treatment setting provides more accurate initial TNM staging and better risk stratification of DTC patients. Post-treatment I-131 imaging is obligatory and must be performed in all DTC patients who receive radioiodine treatment.

Anaplastic and poorly differentiated thyroid carcinomas: genetic evidence of high-grade transformation from differentiated thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD-L1 expression, Sanger sequencing for TERT promoter and RAS mutations, and fluorescence in situ hybridization for ALK and RET rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent TERT promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD-L1, and a lower proportion expressed PAX-8 and TTF-1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs.

Prognostic Significance of KIF-12 Functioning as a Tumour Suppressor in Papillary Thyroid Carcinoma.

Objective: To explore the potential value of a novel marker, KIF-12, in the progression and prognosis of papillary thyroid carcinoma (PTC) through integrative bioinformatics analysis, and clinical sample validation of the prognostic value of KIF-12. Materials and Methods: We extracted the clinicopathological data of 502 PTC patients from The Cancer Genome Atlas-Thyroid Cancer (TCGA-THCA) dataset to identify reliable differentially expressed genes (DEGs) between high and low KIF12 expression groups. Functional enrichment analysis was performed on upregulated DEGs. Gene set enrichment analysis (GESA) was performed to identify the biological pathways. We further applied Cox analysis to determine independent risk factors associated with the PTC progression-free interval (PFI), and a nomogram was established to predict disease outcome. Finally, the prognostic value of KIF12 was validated by means of clinical samples from PTC patients with and without lateral lymph node metastasis. Results: On the basis of the TCGA-THCA database, we found that low KIF-12 expression was significantly related to a higher TNM stage (p<0.05), BRAF mutation status (p = 0.019), and extrathyroidal extension (p<0.001). KIF-12 was an independent prognostic factor of PTC (OR=0.319, 95% CI=0.130-0.784, P=0.013). The prognostic value of KIF12 was also successfully validated in clinical samples from twenty-nine PTC patients with lateral lymph node metastasis by comparison with twenty-two PTC patients without lymph node metastasis (P = 0.004). Conclusions: We report that KIF-12 has a tumor suppressive function in PTC and may be a useful prognostic tool to predict patient outcomes.

Radioiodine whole body scan pitfalls in differentiated thyroid cancer.

PURPOSE: whole body scan (WBS) performed following diagnostic or therapeutic administration of I-131 is useful in patients with differentiated thyroid carcinoma. However, it can be falsely positive in various circumstances. We aimed to report a series of pitfalls in a clinical perspective. METHODS: A search in the database PubMed utilizing the following terms: "false radioiodine uptake" and "false positive iodine 131 scan" has been made in January 2023. Among the 346 studies screened, 230 were included in this review, with a total of 370 cases collected. Physiological uptakes were excluded. For each patient, sex, age, dose of I-131 administered, region and specific organ of uptake and cause of false uptake were evaluated. RESULTS: 370 cases of false radioiodine uptake were reported, 19.1% in the head-neck region, 34.2% in the chest, 14.8% in the abdomen, 20.8% in the pelvis, and 11.1% in the soft tissues and skeletal system. The origin of false radioiodine uptake was referred to non-tumoral diseases in 205/370 cases (55.1%), benign tumors in 108/370 cases (29.5%), malignant tumors in 25/370 cases (6.7%), and other causes in 32/370 cases (8.7%). CONCLUSIONS: WBS is useful in the follow-up of patients with differentiated thyroid carcinoma, however it can be falsely positive in various circumstances. For this reason, it is critically important to correlate the scintigraphic result with patient's medical history, serum thyroglobulin levels, additional imaging studies and cytologic and/or histologic result.

Comparative study between poorly differentiated thyroid cancer and anaplastic thyroid cancer: real-world pathological distribution, death attribution, and prognostic factor estimation.

Background: The clinic-pathological boundary between poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) is unclear due to a wide spectrum of histopathological features and the rarity of the disease. In addition to that, with the highest mortality rate and non-standard treatment modality, the PDTC/ATC population has not been subjected to comprehensive description and comparison with the extent of histological characteristics, therapeutic response, prognostic factors, and death attribution analysis. Method: A total of 4,947 PDTC/ATC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival curve estimation and Cox proportional hazard regression were applied. Results: Overall, the 5- and 10-year DSS for PDTC were 71.9% and 68.0%, respectively, whereas the 5- and 10-year OS are 59.3% and 51.2%, respectively. The median survival time for ATC patients was 3 months with 1-year OS being 26.9% and 1-year DSS being 31.2%. During the follow-up period, 68.1% of the PDTC/ATC cohort were dead, 51.6% of which were attributed to thyroid malignancies and 16.5% to non-thyroid causes. The top three common non-thyroid causes of death were miscellaneous cancers, lower respiratory system disease, and heart disease. The histological feature of papillary thyroid cancer (PTC) was the leading pathological category for PDTC patients (51.7%), whereas 76.7% of ATC patients' pathological feature was characterized as unidentifiable. Sarcoma histological characteristics found in ATC cases suffer the highest overall mortality (vs. PTC, HR = 2.61, 95% CI 1.68-4.06, P < 0.001). Older age unidentifiable histology feature, more advanced AJCC N1b, AJCC M1, and SEER stage, tumor size larger than 5 cm, and more invasive tumor extension were independent bad outcome predictors. Conclusion: The populational analysis of the PDTC/ATC cohort has provided reliable support for better understanding of the difference between PDTC and ATC cases and the guidance of clinical practice and further studies.

Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas.

INTRODUCTION: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients. AIMS: This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. MATERIAL AND METHODS: This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2-ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations (BRAF, RAS, and TERTp) was evaluated. RESULTS/DISCUSSION: All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.

Differentiated thyroid carcinoma: what the nonspecialists needs to know.

Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Papillary thyroid carcinoma tall cell subtype (PTC-TC) and high-grade differentiated thyroid carcinoma tall cell phenotype (HGDTC-TC) have different clinical behaviour: a retrospective study of 1456 patients.

AIMS: Papillary thyroid carcinoma, tall cell subtype (PTC-TC) is a potentially aggressive histotype. The latest World Health Organisation (WHO) classification introduced a novel class of tumours; namely, high-grade differentiated thyroid carcinoma (HGDTC), characterised by elevated mitotic count and/or necrosis, which can exhibit a tall cell phenotype (HGDTC-TC). METHODS AND RESULTS: We analysed the clinical outcomes in a large retrospective cohort of 1456 consecutive thyroid carcinomas with a tall cell phenotype, including PTC-TC and HGDTC-TC. HGDTC-TC is uncommon, accounting for 5.3% (77 of 1379) of carcinomas with tall cell morphology. HGDTC-TC was associated with significantly older age, larger tumour size, angioinvasion, gross extrathyroidal extension, higher AJCC pT stage, positive resection margin and nodal metastasis (P < 0.05). Compared with PTC-TC, HGDTC was associated with a significantly decreased DSS, LRDFS and distant metastasis-free survival (DMFS; P < 0.001). The 10-year DSS was 72 and 99%, the 10-year LRDFS was 61 and 92% and the 10-year DMFS was 53 and 97%, respectively, for HGDTC-TC and PTC-TC. On multivariate analysis, the classification (HGDTC-TC versus PTC-TC) was an independent adverse prognostic factor for DSS, LRDF, and DMFS when adjusted for sex, age, angioinvasion, margin status, AJCC pT and pN stage. CONCLUSIONS: Compared with PTC-TC, HGDTC-TC is associated with adverse clinicopathological features, a higher frequency of TERT promoter mutations (59% in HGDTC-TC versus 34% in PTC-TC) and incurs a significantly worse prognosis. HGDTC-TC is an independent prognostic factor for carcinoma with tall cell morphology. This validates the concept of HGDTC and the importance of tumour necrosis and high mitotic count for accurate diagnosis and prognosis of differentiated thyroid carcinomas.

Wide Composite Resection of Sternal Metastasis & Reconstruction Using Titanium Mesh Implant and Myocutaneous Flap in Differentiated Thyroid Carcinoma: Case Report of Two Cases.

Differentiated Thyroid carcinoma (DTC) with distant skeletal metastases is associated with a very poor prognosis and are unfortunately resistant to radioiodine therapy (RIT). Surgical removal of the metastases in such selected cases is a beneficial adjunct to RIT. We report two cases of DTC with sternal metastases whom we successfully managed with surgical resection of the sternal lesion with reconstruction of the chest wall defect using titanium mesh implant and myocutaneous flap.

Construction and validation of a nomogram for predicting lateral lymph node metastasis in pediatric and adolescent with differentiated thyroid carcinoma.

BACKGROUND: Limited research has been conducted to specifically investigate the identification of risk factors and the development of prediction models for lateral lymph node metastasis (LNM) in pediatric and adolescent differentiated thyroid carcinoma (DTC) populations, despite its significant association with unfavorable prognosis. METHODS: This study entails a retrospective analysis of the clinical characteristics exhibited by pediatric and adolescent patients who have been diagnosed with DTC. The data utilized for this analysis was sourced from the Surveillance, Epidemiology, and End Results (SEER) database, spanning the time frame from 2000 to 2020. Furthermore, the study incorporates patients who were treated at the Departments of Breast and Thyroid Surgery in the Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine, as well as The General Hospital of Western Theater Command, during the period from 2010 to 2020. RESULTS: A cohort of 2631 patients from the SEER database, along with an additional 339 patients from our departments who met the specified inclusion criteria, were included in this study. Subsequently, four clinical variables, namely age, tumor size, multifocality, and extrathyroidal invasion, were identified as being significantly associated with lateral LNM in pediatric and adolescent DTC patients. These variables were then utilized to construct a nomogram, which demonstrated effective discrimination with a concordance index (C-index) of 0.731. Furthermore, the performance of this model was validated through both internal and external assessments, yielding C-index values of 0.721 and 0.712, respectively. Afterward, a decision curve analysis was conducted to assess the viability of this nomogram in predicting lymph node metastasis. CONCLUSION: The current investigation has effectively constructed a nomogram model utilizing visualized multipopulationsal data. Our findings demonstrate a significant association between various clinical characteristics and lateral LNM in pediatric and adolescent DTC patients. These outcomes hold substantial significance for healthcare practitioners, as they can employ this model to inform individualized clinical judgments for the pediatric and adolescent cohorts.

Retrospective case-control study examining the relationship between recurrence-free survival and changes in pre- and post-radioiodine therapy serum thyroglobulin levels in patients with differentiated thyroid cancer.

PURPOSE: Thyroglobulin assay is important to assess the residual or recurrence of differentiated thyroid cancer (DTC). Patients with positive serum thyroglobulin levels after radioactive iodine (RAI) adjuvant therapy could achieve long-term recurrence-free survival (RFS). The patient's prognosis could not be confidently estimated based solely on the evaluation of thyroglobulin levels. We investigated the recurrence rate and RFS of patients who received adjuvant RAI therapy after surgery for DTC to clarify the relationship between changes in pre- and post-therapy serum thyroglobulin levels and RFS. MATERIALS AND METHODS: Patients who underwent adjuvant RAI therapy between May 2007 and March 2021 were included in this study, whereas those with positive anti-thyroglobulin antibodies, distant metastases, or gross residual tumors were excluded. The change in pre- and post-treatment serum thyroglobulin levels under thyroid-stimulating hormone stimulation was calculated and classified as follows: group A, thyroglobulin levels decreased by ˃10%; group B, thyroglobulin levels within a range of 10% or less; and group C, thyroglobulin levels increased by ˃10%. RFS outcomes were analyzed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, and multivariate analysis was performed using the Cox proportional hazard model. RESULTS: A total of 74 patients were included. Relapse was seen in 13 of 46 patients in group A, 9 of 15 in group B, and 10 of 13 in group C. Median RFS was 129.00 (95% confidence interval CI 77.79-180.21), 113.00 (95% CI 86.83-139.17), and 33 months (95% CI 6.026-59.974) in groups A, B, and C, respectively. Patients in group C exhibited significantly shorter RFS than those in groups A and B (P = 0.001). CONCLUSIONS: Changes in thyroglobulin levels pre- and post-therapy were associated with RFS. Patients with decreased post-therapy thyroglobulin levels had a favorable prognosis, even if their thyroglobulin levels were positive after RAI therapy.

Sufficiency of a Single Negative Thyroglobulin Standard for Judging the Success of Ablation in Low- and Intermediate-risk Differentiated Thyroid Cancer: A Retrospective Study.

BACKGROUND: We investigated how reduced successful ablation criteria may be used to evaluate radioiodine remnant ablation in patients with low- and intermediate-differentiated thyroid carcinoma (DTC). METHODS: Overall, 254 low- and intermediate-risk patients with DTC were categorized into three groups (positive, weak, positive, and negative) on the basis of a visual study of thyroid imaging performed before postoperative iodine treatment. Semi-quantitative analysis parameters were incorporated into the positive Tc-99m pertechnetate scanning to further examine the clinical use of thyroid imaging. We investigated the value of successful judgment criteria and the influencing factors of radioiodine ablation. At the same time, the predictive value of thyroglobulin (Tg) for radioiodine treatment and the overall clinical efficacy were assessed. RESULTS: A total of 250 (98.43%) patients were identified as having functional thyroid tissue residue on the Tx-whole-body scan, and 137 (53.94%) patients had positive Tc-99m pertechnetate scans using semi-quantitative analysis. The single Tg standard could not substitute the double standard (χ! !=22.042, p<0.001) for patients with residual thyroid weight by a semiquantitative analysis. However, the semi-quantitative analysis revealed no association between 99mTcO4-thyroid scan and ablation treatment using semi-quantitative analysis; only preablation sTg levels were related with success in the multivariate logistic regression analysis, with a cut-off value of 2.88 ng/mL. The pre-ablation stimulated Tg level was also the primary factor of satisfactory response following follow-up with an optimal cut-off of 6.506 ng/mL. CONCLUSION: Even in low- and intermediate-risk patients with DTC, a single negative Tg standard also requires receiving some restrictions in the evaluation of ablation success and is inadequate. Conventional 99mTcO4 thyroid imaging combined with a quantitative analysis program can improve the clinical practice of single negative Tg standard.

Expanding Our Knowledge of DICER1 Gene Alterations and Their Role in Thyroid Diseases.

Mutations in DICER1, a gene involved in RNA interference, have been associated with a wide range of multi-organ neoplastic and non-neoplastic conditions. Historically known for its association with pleuropulmonary blastoma, DICER1 syndrome has received more attention due to the association with newly discovered diseases and tumors. Recent studies evaluating DICER1 mutations and DICER1-driven thyroid disease in both pediatric and adult thyroid nodules revealed thyroid disease as the most common manifestation of DICER1 mutations. This study undertakes a comprehensive investigation into DICER1 mutations, focusing on their role in thyroid diseases. Specific attention was given to thyroid follicular nodular disease and differentiated thyroid carcinomas in infancy as highly indicative of germline DICER1 mutation or DICER1 syndrome. Additionally, poorly differentiated thyroid carcinoma and thyroblastoma were identified as potential indicators of somatic DICER1 mutations. Recognizing these manifestations should prompt clinicians to expedite genetic evaluation for this neoplastic syndrome and classify these patients as high risk for additional multi-organ malignancies. This study comprehensively synthesizes the current knowledge surrounding this genetically associated entity, providing intricate details on histologic findings to facilitate its diagnosis.

Body composition changes in patients with differentiated thyroid cancer after iodine-131 treatment and short-term levothyroxine replacement and suppression therapy.

PURPOSE: The purposes of this study were to assess the changes in body composition in patients who underwent thyroidectomy due to differentiated thyroid cancer (DTC) after radioactive iodine therapy (RAI) and short-term levothyroxine (LT4) supplementation and to explore the correlations between body composition distribution and corresponding blood indices. METHODS: Fifty-seven thyroidectomized DTC patients were included. Serum was tested for several biochemical indices of thyroid function, lipids, and bone metabolism, and body composition parameters were measured via dual-energy X-ray absorptiometry before and 4-6 weeks after RAI and LT4 supplementation. RESULTS: The body composition of DTC patients changed after RAI. Fat mass in all parts of the body decreased (range of relative change (RRC) -12.97--2.80%). Bone mineral content (BMC) increased throughout the body (relative change (RC) 12.12%), head (RC 36.23%), pelvis (RC 9.00%), and legs (RC 3.15%). Similarly, bone mineral density (BMD) increased in different regions (RRC 3.60-26.43%), except for the arms. Notably, lean mass in the arms (RC 4.30%) and legs (RC 3.67%) increased, while that in the head decreased (RC -2.75%), while total lean mass did not change at 4-6 weeks after LT4 supplementation. Furthermore, changes in fat distribution in the android region were related to the changes in total cholesterol (r = -0.390) and low-density lipoprotein cholesterol (r = -0.354), and changes in the BMC and BMD of the lumbar spine were positively associated with the changes in calcitonin (r = 0.302 and 0.325, respectively). CONCLUSIONS: After RAI and short-term LT4 supplementation in DTC patients, body composition rapidly and positively changed and was characterized by decreased fat mass and increased BMC and BMD.

Clinicopathologic Characteristics of Thyroid Microcarcinoma: Findings from a Hospital-Based Study in Vietnam.

BACKGROUND: Thyroid microcarcinoma (TMC) incidence has significantly increased in recent decades. The rates of lymph node metastasis extrathyroidal extension have been significantly different in patients with TMC ≤5 mm versus those with size >5 mm. The current analysis aimed to examine the clinicopathologic features of TMC measuring <5 mm and to compare them with those of TMC ≥5 mm. METHODS: A total of 273 patients with TMC confirmed by histological examination from December 2020 to May 2021 were enrolled in Bach Mai Hospital, Hanoi, Vietnam. Unconditional logistic regression models were used to determine the association between clinicopathological factors and tumor size, central lymph node metastasis and extrathyroidal extension. RESULTS: We found 212/273 patients (77.7%) were diagnosed incidentally. The majority of patients were female (87.5%) and had a mean age of 44.2 years. The mean tumor size (±standard deviation (SD)) was 5.72 ± 2.33 mm. Most of the patients were also diagnosed with papillary TMC. Multifocal and bilateral lesions accounted for 13.2% and 12.1%, respectively. The extrathyroidal invasion was observed in 14.7% (40 patients), while 24.5% (67 patients) were those with central lymph node metastases. The rate of extrathyroidal extension in patients with tumor size ≥5 mm was significantly higher than in patients with tumor size <5 mm (odds ratio (OR) = 4.98; 95% confidence interval (CI): 1.48-16.70; p = 0.004). Patients with body mass index (BMI) <23 kg/m2 were found to be protected against the odds of extrathyroidal extension (OR = 0.38, 95% CI: 0.19-0.75; p = 0.004) compared to those with BMI ≥23 kg/m2. In univariable mode, central lymph node metastasis was positively associated with the odds of the presence of extrathyroidal extension (OR = 2.70, 95% CI: 1.34-5.45; p = 0.004). In the multivariable model, central lymph node metastasis was also associated with the presence of extrathyroidal extension (OR = 2.507, 95% CI: 1.194-5.264; p = 0.017). Univariate analysis demonstrated that tumor size ≥5 mm (OR = 2.04; 95% CI: 1.01-4.17; p = 0.047) and extrathyroidal extension (OR = 2.71; 95% CI: 1.34-5.45; p = 0.004) were risk factors of central cervical lymph node metastasis. In multivariable models, the extrathyroidal extension was associated with central lymph metastasis. CONCLUSIONS: TMC <5 mm tumor size is less likely to have aggressive characteristics, including extrathyroidal extension, than a TMC ≥5 mm. Long-term follow-up studies are thus warranted to investigate the factors in the prognosis of TMC.

Clinicopathological features of differentiated thyroid carcinoma as predictors of the effects of radioactive iodine therapy.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis; however, 5 %-15 % develop radioactive iodine-refractory (RAIR) DTC (RAIR-DTC), which has a poor prognosis and limited treatment options. The aim of the present study was to investigate the clinicopathological characteristics of RAIR-DTC in order to provide clinical evidence for timely prediction of the effects of iodine therapy. METHODS: Clinicopathological data for 44 patients with RAIR-DTC and 50 patients with radioiodine-avid DTC (RAIA-DTC) were retrospectively analyzed. The risk factors for RAIR-DTC were evaluated and a RAIR-DTC prediction model was established. RESULTS: RAIR-DTC showed unique clinicopathological features that differed from those of RAIA-DTC; these included age >55 years, a high-risk histological subtype, a large tumor size, a late TNM stage, calcification, distant metastasis, and more than six metastatic lymph nodes. Patients with RAIR-DTC also developed earlier tumor progression. Binary logistic regression analysis showed that distant metastasis, a high-risk histological subtype, and a maximum tumor diameter of ≥12.5 mm were independent risk factors for RAIR-DTC, and the specificity and sensitivity of a combination of these three parameters for the prediction of RAIR-DTC were 98.0 % and 56.8 %, respectively. Decision curve analysis and the calibration curve revealed that the combined prediction of these three parameters had good repeatability and accuracy. CONCLUSION: The clinicopathological features of DTC can effectively predict the effects of iodine therapy. A combination of distant metastasis, a high-risk histological subtype, and a maximum tumor diameter of ≥12.5 mm showed significantly higher prediction accuracy.

Thyroid cancer necrosis not evident on imaging: A cautionary case series on poorly differentiated thyroid carcinoma diagnosed only on final pathology.

OBJECTIVE: Poorly-differentiated thyroid cancer (PDTC) is a highly aggressive malignancy which is recently defined and understudied in the radiologic literature. Necrosis is a key histopathologic criterion for the diagnosis of PDTC. We illustrate the current difficulty in accurate identification of histopathologic necrosis on preoperative imaging. METHODS: A series of seven patients with the final diagnosis of PDTC from our institution were identified. Multimodality preoperative imaging was analyzed by two head and neck radiologists. Final pathology reports were queried confirming histopathologic evidence of necrosis. RESULTS: Patients presented with a wide range of preoperative imaging features. A consistent imaging appearance confirming necrosis was not identified. All patients were subsequently upstaged to PDTC following final pathological analysis. CONCLUSION: A lack of definitive evidence of necrosis on preoperative imaging does not exclude the possibility of PDTC. We demonstrate the need for further research to establish a clear methodology for the preoperative diagnosis of PDTC.

Thyroglobulin Antibody (TgAb) Positive is an Independent Risk Factor for Lymph Node Metastasis in Patients with Differentiated Thyroid Carcinoma.

Objective: To investigate the relationship between lymph node metastasis and the clinicopathologic features of differentiated thyroid carcinoma (DTC) patients with thyroglobulin antibody (TgAb) positive and negative. Methods: A total of 443 patients with DTC were included in this study. Clinicopathological data of the patients were collected, including tumor size, clinical stage, calcification, Hashimoto's thyroiditis, extra-membrane infiltration, BRAF V600E mutation status, and thyroid-related hormone and antibody levels. The relationship between of lymph node metastasis and clinicopathologic features was analyzed. Results: There were 227(51.2%) TgAb negative and 216(48.8%) TgAb positive DTC patients. Compared with patients without lymph node metastasis, DTC patients with lymph node metastasis had a higher proportion of patients with <55 years of age, maximum tumor diameter >1cm, calcification, BRAF V600E mutation, and TgAb positive. Multivariate regression logistic analysis showed that <55 years old (odds ratio (OR): 2.744, 95% CI: 1.665-4.522, P<0.001), maximum tumor diameter >1cm (OR: 2.163, 95% CI: 1.431-3.271, P<0.001), BRAF V600E mutation (OR: 2.489, 95% CI: 1.397-4.434, P=0.002), and TgAb positive (OR: 1.540, 95% CI: 1.020-2.326, P=0.040) were risk factors for lymph node metastasis. Maximum tumor diameter >1cm and BRAF V600E increased the risk by more than one fold for lymph node metastasis in TgAb-negative and TgAb-positive DTC patients. Conclusion: Younger age (<55 years old), maximum tumor diameter >1cm, BRAF V600E mutation, and TgAb positive were independent risk factors for lymph node metastasis in DTC. And maximum tumor diameter >1cm and BRAF V600E mutation were risk factors for lymph node metastasis both in TgAb positive and negative DTC patients.